Photodynamic therapy for prostate cancer

Photosensitive chlorin E6 combats individual tumor cells

In Chlorin E6 photodynamic therapy for prostate cancer, the tumor cells are irradiated with monochromatic, red laser light, which causes the tumor cells to die.
(Photo: Clinic for Prostate Therapy, Heidelberg)

Photodynamic therapy (PDT) is a form of cancer therapy using light. With its help, malignant tumors can be diagnosed and treated in a very targeted manner. It has already been proven effective for many forms of cancer – such as skin cancer, bladder, lung and bile duct carcinomas. Treatment successes are also known for breast cancer and brain tumors.
Until now, there has been no possibility of using this special form of PDT for prostate cancer. However, at the Heidelberg Clinic for Prostate Therapy, the procedure is being used for the first time in the world with a special photoactive substance, Chlorin E6, produced at the Heidelberg Technology Park on the Unicampus. The Heidelberg Clinic for Prostate Therapy has now developed a procedure to use this novel therapy for this common disease as well.

What is Chlorin E6?

Chlorin E6 trisodium salt, or Ce6 for short, is a so-called photosensitizer that accumulates specifically in tumor tissue. The green porphyrin is produced from plant material by Synverdis GmbH (www.synverdis.de) in accordance with the guidelines of the pharmaceutical industry under GMP conditions (Good Manufacturing Practice).
The substance has already been successfully tested in a phase IIb clinical trial for the treatment of central bronchial carcinoma. In the available studies and experiences in the context of curative trials, Chlorin did not show any serious side effects. It is said not to have any dark toxicity.
The active ingredient Chlorin E6 is produced by Synverdis GmbH in a production facility in the Heidelberg Technology Park and then manufactured as a formulation individually for each patient.
Around half a dozen different photosensitizers, i.e. photosensitive substances, are used worldwide in various cancer therapies.
The principle of PDT is most widely established in dermatology. Here, the photoactive substance is usually applied externally to the skin in the form of ointments. Then the affected area is irradiated from the outside with special laser light.

How does photodynamic therapy work for prostate cancer using Chlorin E6?

The symbolic image shows an accumulation of tumor cells.
The chlorin E6 trisodium salt is a so-called photosensitizer that selectively accumulates in neoplastic tissue, shown here in green.
As early as 30 minutes after the administration of Chlorin E6, the red fluorescence radiation can be used in diagnostics for the localization of cancer cells.
The oxygen reacts immediately with components of the tumor cell and triggers a cell-damaging effect in the tumor. This ultimately leads to the death (necrosis) of the tumor.
(Illustrations: Synverdis GmbH, Heidelberg)

The patient is injected with a drug containing the photoactive substance, chlorin E6, as a short infusion. This substance accumulates 20 times more in tumor tissue than in healthy cells.
If monochromatic laser light of a certain wavelength (in this case red light with a wavelength of 665 nanometers) then reaches the chlorin E6 within the tumor cells, the energy of the laser light is transferred to the photosensitizer chlorin E6. This absorbed energy is released to the surrounding oxygen molecules, producing so-called singlet oxygen (1O2). This oxygen molecule is highly reactive and reacts with all biological components in the tumor cell such as the cell nucleus, mitochondria and cell membrane. The tumor cell loses its structure and dies – similar to chemotherapy but highly selective.
Any surrounding cells without Ce6 in the direct vicinity remain largely unaffected by the red laser light, as the laser light can only exert its effect in combination with the light-active substance.
Depending on the tumor situation, the laser fibers are positioned, guided by ultrasound, via the perineum in the prostate region or the tumor tissue is reached by means of a cystoscopy, since the laser light has a penetration depth of approximately 2 cm. Both forms of surgery are performed under a short anesthesia.

Are there comparable treatment methods in medicine?

Photodynamic therapy is considered a focal therapy, namely, a therapy that does not treat a complete organ but is limited to the tumor as specifically as possible. These therapies also include the HIFU method with the Sonablate 500 or the Irreversible Electroporation (IRE) procedure with the NanoKnife. In addition, there is also the so-called Tookad method, which is already being used at some hospitals. However, the photosensitizer used here does not lead to a particularly high accumulation in the tumor cells. Irradiation with laser light leads to occlusion of the tumor vessels supplying the cells. It is not the individual tumor cell that is thus caused to die, but rather a part of the prostate.
PDT using Chlorin E6, on the other hand, attacks the individual tumor cell and only this.
The neighboring, healthy tissue remains largely unaffected.
This opens up completely new treatment options. For example, in certain cases where the bladder sphincter has been affected by tumor cells, the function of this sphincter could be preserved because only the tumor cells are killed and not the muscle cells necessary for the function.

In photodynamic diagnostics (PDD) (left part of figure), tumor cells are virtually stained, for example, in the case of a bladder tumor. The fluorescent dye is introduced into the bladder via a catheter, in the case of chlorin via infusion. The dye is absorbed more strongly by tumor cells and then leads to improved visualization of the tumor area during bladder endoscopy, especially when the tissue is irradiated with blue light. This is referred to as fluorescence endoscopy. Subsequently, the tumor can be removed by conventional methods, e.g. by surgical operation.
With Chlorin E6, photodynamic therapy (PDT) is also possible afterwards (right part of the figure). Three hours after the injection of Ce6, the tumor cells will have taken up the substance. Irradiation with special laser light triggers a chemical reaction in the tumors that produces singlet oxygen, which in turn causes the tumor cells to die.
(Fig.: Synverdis GmbH, Heidelberg)

For which prostate cancer patients is photodynamic therapy particularly suitable?

In contrast to surgical, chemo- or radiotherapeutic procedures, PDT represents the significantly lower burden for the patient. Furthermore, the basic efficacy of PDT has long been studied for certain skin tumors and the success of the method has been proven.
The Clinic for Prostate Therapy in Heidelberg has a unique selling point worldwide to date with prostate cancer treatment using PDT and Chlorin E6. However, long-term studies on the long-term course of cancer after PDT of the prostate are not yet available. Therefore, the new procedure is particularly suitable for patients who are considered "beyond treatment" in the conventional medical sense or for patients who reject conventional therapies.